Safety of acamprosate for alcohol use disorder after liver transplant: A pilot randomized controlled trial.

Acamprosate is a therapy for alcohol use disorder, but data on feasibility and safety in recipients of liver transplants are lacking. This was a single-center unblinded prospective pilot randomized controlled trial of adults (≥18 y) with liver transplant for alcohol-associated liver disease enrolled between 2021 and 2023, who were randomized 2:1 to the intervention of acamprosate (666 mg dose 3 times daily) or standard of care (SOC) over 14 weeks. Outcomes included safety (prevalence of adverse events [AEs]), feasibility (weekly survey response rate >60%), adherence (self-reported acamprosate use >60%), and efficacy (reduction in Penn Alcohol Craving Scale), and relapse-blood phosphatidylethanol (≥20 ng/mL/reported alcohol use) evaluated by standardized weekly surveys. The efficacy analysis was done in both the intention-to-treat (excluding withdrawals before medication administration) and per-protocol population (excluding withdrawals/<4 weeks participation). Of 78 participants who were approached, 30 enrolled (19 acamprosate and 11 SOC) with similar baseline characteristics. Eight participants withdrew (6 acamprosate before medication administration and 2 SOC). AEs were similar between acamprosate and SOC groups (92.3% vs. 90.0%, p > 0.99), including grade 3 AEs (53.9% vs. 60.0%, p > 0.99) with no reported grade 4/5 AEs. Survey response rates were similar in acamprosate versus SOC groups (61.0% vs. 76.0%, p = 0.19), and 69.0% were acamprosate adherents. Baseline Penn Alcohol Craving Scale values were low with no difference by the group in median absolute change in Penn Alcohol Craving Scale for intention-to-treat (0, IQR: -4 to 0 vs. 0, IQR: 0-0, p = 0.32), and per-protocol analyses (-1, IQR: -6 to 0 vs. 0, IQR: -0 to 0, p = 0.36). There was no reported or biochemical evidence of alcohol relapse. In this pilot study, preliminary data suggest that acamprosate may be safe and feasible. These data can inform larger studies and clinician efforts to address alcohol use disorder in post-liver transplant care (ClinicalTrials.gov, Number: NCT06471686).